Vasopressin Mediates α1-Adrenergic Stimulation of Adrenocorticotropin Secretion*

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Abstract
In conscious rats bearing venous and cerebroventricular cannulae, central administration of the .alpha.1-adrenergic agonist methoxamine stimulated the secretion of ACTH, and the effect was reduced by the .alpha.1-antagonist prazosin. Methoxamine was more potent in stimulating ACTH secretion when injected icv than peripherally, suggesting that the stimulant .alpha.1-adrenoceptors are located in the brain rather than in the periphery. In order to investigate the relative roles of hypothalamic CRF-41 and vasopressin as mediators of the stimulant effects of .alpha.1-adrenoceptors on ACTH secretion, we examined the effects of equipotent doses of antagonists to CRF-41 and vasopressin on the ACTH response to methoxamine. The effect of methoxamine was reduced by the vasopressin antagonist dPTyr(Me) arginine vasopressin but not by the CRF-41 antagonist .alpha.-helical CRF-9-41, suggesting that vasopressin is more important than CRF-41 in mediating the effects of .alpha.1-adrenoceptors on ACTH secretion. However, the combination of the two antagonists caused a reduction in the ACTH response to methoxamine that was greater than that of the vasopressin antagonist alone. This suggested that CRF-41 plays some role in this response, possibly by enhancing the activity of vasopressin in a synergistic manner. These two hypothalamic peptides seem to account for most of the ACTH releasing activity of .alpha.1 adrenoceptor activation.